Ampullary Carcinoma

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Practice Essentials

Ampullary carcinoma is a rare malignant tumor originating at the ampulla of Vater, in the last centimeter of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla. Patients typically present with symptoms related to biliary obstruction. A high index of suspicion is paramount so that the appropriate laboratory and imaging studies may be obtained to facilitate early diagnosis.

Over the last decade, advances in technology have allowed improvements in the diagnosis and staging of this disease. Current imaging techniques enable more accurate staging of these tumors and permit preoperative determination of which tumors are surgically resectable.

Surgical resection with pancreaticoduodenectomy remains the gold standard for treatment, although local excision is an option for patients who may be unable to tolerate this. Several palliative options exist for patients with unresectable or metastatic disease. While certain features (eg, positive resection margins and lymph node positivity) portend poorer prognosis, patients with ampullary cancer generally have better overall survival than patients with pancreatic cancer.

Signs and symptoms

The signs and symptoms of ampullary carcinoma are largely related to obstruction of the bile duct or pancreatic duct. They include the following[1] :

See Presentation for more detail.

Diagnosis

Laboratory studies

Routine laboratory studies include the following:

Ultrasonography of the abdomen

CT scanning of the abdomen and/or pelvis

Other imaging studies

See Workup for more detail.

Management

The standard surgical approach to the treatment of ampullary carcinoma is pancreaticoduodenal resection (Whipple procedure). The procedure involves en bloc resection of the gastric antrum and duodenum; a segment of the first portion of the jejunum, gallbladder, and distal common bile duct; the head and often the neck of the pancreas; and adjacent regional lymph nodes.

The operative mortality rate for pancreaticoduodenectomy was at one time reported to be approximately 20%, but several hospital centers have since reported large series with operative mortality rates in the range of 5%.

See Treatment for more detail.

Background

Carcinoma of the ampulla of Vater is a malignant tumor arising in the last centimeter of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla. The pancreatic duct (of Wirsung) and common bile duct merge and exit by way of the ampulla into the duodenum. The ductal epithelium in these areas is columnar and resembles that of the lower common bile duct.

Adenocarcinoma of the ampulla of Vater is relatively uncommon, accounting for approximately 0.2% of gastrointestinal tract malignancies and approximately 7% of all periampullary carcinomas.

Pathophysiology

The periampullary region is anatomically complex, representing the junction of 3 different epithelia, pancreatic ducts, bile ducts, and duodenal mucosa. Grossly, carcinomas originating in the ampulla of Vater can arise from 1 of 4 epithelial types: (1) terminal common bile duct, (2) duodenal mucosa, (3) pancreatic duct, or (4) ampulla of Vater.

Distinguishing between true ampullary cancers and periampullary tumors is critical to understanding the biology of these lesions. Each type of mucosa produces a different pattern of mucus secretion. In a complete histochemical study, Dawson and Connolly divided acid mucins into sulphomucins and sialomucins; in general, ampullary cancers produce sialomucins, whereas periampullary tumors secrete sulfated mucins. These researchers demonstrated that ampullary tumors secreting sialomucins had a better prognosis (100% vs 27% 5-y survival rate).[2] Other investigators have confirmed the prognostic power of the pattern of mucin secretion.

Carter et al suggest that, histologically, ampullary tumors can be classified as either pancreaticobiliary or intestinal, and that the clinical behavior of these tumors reflects this classification; the course of intestinal ampullary adenocarcinomas is similar to that of their duodenal counterparts, whereas pancreaticobiliary tumors follow a more aggressive course, similar to that of pancreatic adenocarcinomas.[3]

Immunohistochemical stains for expressions of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, Ki-67, and p53 have been studied for prognostic power. In a series of 45 patients, expression of CA 19-9 labeling intensity and apical localization both were statistically significant predictors of poor prognosis. The 5-year survival rates were markedly different between tumors that expressed CA 19-9 and those that did not (36% vs 100%).[4] CEA expression also might be a marker for prognosis, but it is much weaker. Ki-67 and p53 were not demonstrated to have an effect on outcome. Research along these avenues ultimately might provide the rationale for discriminative administration of adjuvant therapy.

Epidemiology

Frequency

United States

Adenocarcinoma of the ampulla of Vater is a relatively uncommon tumor that accounts for approximately 0.2% of gastrointestinal tract malignancies and approximately 7% of all periampullary carcinomas. A review of data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program found 5,625 cases of ampullary cancer between 1973 and 2005; the frequency of the disease has been increasing since 1973.[5]

Mortality/Morbidity

Pancreaticoduodenectomy is a formidable operation, and the morbidity and mortality rates associated with this procedure historically have been high.

Until recently, the operative mortality rate was reported to be approximately 20%. In the past few years, several centers have reported large series with an operative mortality rate in the range of 5%. A review of the last 130 pancreaticoduodenectomies performed at Stanford University Medical Center over the previous 5 years revealed an operative mortality rate of 3%. This improvement can be attributed to increased surgical experience, improved patient selection, improved anesthesia, better preoperative imaging, and general improvement in the management of ill patients.

The morbidity rate associated with the surgery is approximately 65%. In some series, 13% of patients required a repeat laparotomy for complications. Patients may experience fistula formation, delayed intestinal function, pneumonitis, intra-abdominal infection, abscess, or thrombophlebitis. Marginal ulceration, diabetes, pancreatic dysfunction (steatorrhea), and gastrointestinal motility disorder all can manifest as late complications of the surgery.

Race- and sex-related demographics

Because carcinoma of the ampulla of Vater is relatively uncommon, studies of the patterns of occurrence among different ethnic groups have not been conducted.

Ampullary cancer is more common in men, according to the National Cancer Institute’s SEER Program.[5]

History

The most common clinical manifestation of ampullary carcinoma is jaundice, which occurs due to obstruction of the biliary tract by the tumor. Patients may also experience scleral icterus and pruritus because of obstruction of the bile duct. Other common complaints include dyspepsia, anorexia, malaise, and weight loss.

Pancreatitis may sometimes be the initial clinical presentation due to pancreatic duct obstruction. Patients may therefore complain of symptoms of pancreatitis, such as epigastric/mid-abdominal pain, back pain, nausea, and vomiting.

Diarrhea, a common but not universal symptom, might be associated with an absence of lipase within the gut because of pancreatic duct obstruction.

Physical

See the list below:

Laboratory Studies

Routine laboratory studies include the following:

A rising bilirubin level due to obstructive jaundice often is the sole presenting sign.

CA 19-9 is a serum tumor marker that is often elevated in pancreatic malignancies and might have a role in assessing response to therapy, predicting tumor recurrence, or both.

CEA is another nonspecific tumor marker that sometimes is elevated in pancreatic malignancies. It might have a role in assessing response to treatment or predicting tumor recurrence. Because CEA also is elevated in patients with other gastrointestinal malignancies (in particular, colon and rectal cancer), the possibility of a second primary tumor needs to be excluded in these patients.

Imaging Studies

Ultrasonography

Abdominal ultrasound is the initial study to evaluate the common bile duct or pancreatic ducts. Dilatation of these ducts essentially is diagnostic for extrahepatic obstruction and can explain abdominal pain, even in patients with localized and noninvasive disease. However, 10-15% of patients with normal common bile duct findings on ultrasonography demonstrate extrahepatic biliary obstruction on a computed tomography (CT) scan. Both ultrasound and CT can help reveal metastatic disease in the liver or regional lymph nodes.

Computed tomography

Obtain a CT scan image to evaluate the local region of interest (abdomen, pelvis, or both) and evaluate for possible metastases. CT scan often demonstrates a mass but is not helpful in differentiating ampullary carcinoma from tumors of the head of the pancreas or periampullary region. If the lesion is smaller than 2 cm, pancreatic or bile duct dilation might be the only abnormalities noted on CT scan. Such findings are highly suggestive of pancreatic malignancy and require further evaluation, usually with endoscopic retrograde cholangiopancreatography (ERCP).

Dynamic CT scanning (ie, high-speed scans obtained during rapid intravenous administration of iodinated contrast material) can reveal tumor involvement of the vasculature. Some centers still rely on angiography to help identify patients with potentially resectable disease.

Endoscopic ultrasound

Endoscopic ultrasound (EUS) is often used as a part of the local staging. EUS allows visualization of the duodenal wall, ampulla, bile duct, and pancreatic duct, as well as regional lymph nodes. EUS can facilitate biopsy of the tumor via fine needle aspiration (FNA) and is also used to evaluate regional lymph nodes for lymph node metastasis. Lastly, EUS allows visualization of celiac and superior mesenteric vessels to evaluate for vascular invasion.

In one series evaluating the use of EUS to predict resectability and need for palliative treatment in patients with pancreatic or ampullary cancer, EUS demonstrated a 50% sensitivity, 100% specificity, 100% positive predictive value, 61% negative predictive value, and 72% accuracy[6] .

Intraductal ultrasonography has been reported by some to more accurately visualize tumor infiltration into the duodenal wall and ampulla.

Endoscopic retrograde cholangiopancreatography

Obtain ERCP to evaluate the ductal architecture further. The following findings on ERCP suggest pancreatic cancer:

Chest radiograph

Obtain a chest x-ray film to complete the workup (ie, for staging purposes).

Positron emission tomography

Positron emission tomography (PET) or PET-CT scans have been widely adopted in the author's clinic as a means of imaging the metabolic activity of a particular tumor. PET or PET-CT scans can detect metastases that are too small to be reliably detected on a CT scan.

Staging

Over the years, multiple systems for staging this tumor have been proposed. Martin proposed a 4-stage system, as follows:

The classification system of Yamaguchi and Enjoji is similar to the Martin classification.[7]

Talbot et al devised a system that scored tumors according to the degree of infiltration (from 1-4 according to increasing infiltration) and according to tumor differentiation (from 1-3 for well, moderately, and poorly differentiated tumors), the sum of which separated the patients into 2 groups (scores 2-4 and scores 5-7).[8]

The currently accepted American Joint Committee on Cancer staging system (7th edition) for ampullary carcinoma emphasizes the importance of pancreatic invasion and lymph node metastases (see below and see Table 1, below). Size has little impact on tumor stage. The definition of primary tumor (T), regional lymph node (N), and remote metastases (M) for classification and staging of cancer of the ampulla of Vater is provided below.

Primary tumor is defined as follows:

Regional lymph nodes are defined as follows:

Distant metastases are defined as follows:

Table Staging of Ampullary Cancers by the TNM System.



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See Table

 

Surgical Care

The standard surgical approach is pancreaticoduodenal resection (Whipple procedure). The procedure involves en bloc resection of the following:

In a review of 450 cases of surgical resection of ampullary adenoma or adenocarcinoma at Johns Hopkins, Winter et al found that 96.7% of the patients had undergone pancreaticoduodenectomy rather than local excision. These researchers concluded that pancreaticoduodenectomy should be the preferred approach for most ampullary neoplasms that require surgical resection, given that nearly 30% of the Johns Hopkins patients with T1 disease had lymph node metastases.[9]

Factors associated with the presence of lymph node metastasis included the following[9, 10] :

Results after radical resection of ampullary of Vater carcinoma have been improving. During recent decades, 5-year survival rates have ranged from 20-61%, averaging higher than 35%. The reported mortality rates from this operation are decreasing. A summary follows in Table 2, below.

Table 2. Results of Pancreaticoduodenal Resection for Carcinoma of the Ampulla of Vater



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Resectability

In a review of more than 1100 patients published in a surgical series, Howe et al reported that the overall rate of resectability was 82%.[20] This most likely overestimates the true resectability rate because patients in whom radiologic studies identify unresectable disease often are not included in retrospective surgical series.

A review of cases from Veterans Affairs hospitals across the United States by el-Ghazzawy et al revealed that only 63% of presenting patients undergo surgery for cure. At disease presentation, 30-50% have involved lymph nodes.[16]

A few studies have been conducted on the pattern of lymphatic spread of ampullary cancer. These studies have been difficult to interpret because of the lack of standardized nomenclature for lymph node groups, variability in the degree of superior mesenteric lymph node dissection, and the small number of patients.

Shirai and colleagues meticulously reviewed 21 cases of ampullary cancer and documented the pattern of lymphatic spread. The site of greatest nodal involvement, the first echelon group, is the posterior pancreaticoduodenal nodal group. The nodal groups surrounding the inferior pancreaticoduodenal artery were the superior mesenteric lymph nodes involved most often. Finally, the para-aortic lymph node groups were involved in 3 patients with resectable disease.[22]

Kayahara reported that the inferior pancreaticoduodenal nodes (13b) and the superior mesenteric nodes (14) were the groups most often involved with metastatic carcinoma.[23]

Local excision

Because of the mortality and morbidity associated with pancreaticoduodenectomy, surgeons have studied local excision of cancers of the ampulla of Vater to avoid major resection. Transduodenal excision of ampullary tumors has been proposed as an intermediate option between radical resection and palliative bypass for high-risk patients. However, this approach remains highly controversial.

Local resection has generally been reserved for poor operative candidates (eg, elderly patients, those with other comorbid conditions) with favorable tumors (generally <2 cm, polypoid). Unfortunately, this approach compromises local control and has a higher risk of a positive margin, possibly requiring repeat excisions and resulting in higher local recurrence rates of up to 30%[24] . Additionally, lymph node metastasis may be present even in patients with T1 tumors and local resection does not include a regional lymphadenectomy, as is performed with pancreaticoduodenectomy.

Some have argued that local resection is simpler, is better tolerated and may have acceptable survival rates. In a series of 21 patients who underwent local resection of ampullary adenomas, Posner et al demonstrated overall survival of 85% and no tumor recurrence in 89% of the surviving patients (with average follow up of 38 months). However, this study was not limited to ampullary cancer; final pathology demonstrated 1 patient (5%) with invasive cancer, 2 (9%) with microinvasive cancer, 6 (28%) with high-grade dysplasia, and 1 (5%) with low-grade dysplasia.[25] .

Carcinoma in situ has been diagnosed with increasing frequency. It has been associated with polypoid growth and may be treated with endoscopic polypectomy. In these circumstances, the entire polyp should be removed and the base of the polyp should be carefully examined to ensure that no cancer is at the margin. In the case of an incomplete excision, a prompt pancreaticoduodenectomy is essential. Patients who undergo polypectomy only should be monitored endoscopically at yearly intervals to detect any recurrence.

Staging of ampullary cancer is critical to treatment. While ampullary polypectomy and ampullectomy have been performed successfully on some patients with ampullary cancer, local resection as a therapeutic approach is best reserved for patients with benign lesions, such as ampullary adenomas, or patients with carcinoma in situ or T1 tumors whose overall performance status makes the risks associated with a formal pancreaticoduodenectomy excessive. In general, for ampullary carcinoma, pancreaticoduodenectomy remains the gold standard and should be offered as long as the patient is able to tolerate the operation.[1]

Adjuvant Therapy

Because local and systemic failures remain problematic, physicians continue to be interested in offering adjuvant therapy. The relative rarity of this disease limits research in this area.[26, 27]

Willett and colleagues summarized their experience with adjuvant radiotherapy for high-risk tumors of the ampulla of Vater (risk factors included invasion into the pancreas, poorly differentiated histology, involved lymph nodes, or positive resection margins).[28] Twelve patients received adjuvant radiotherapy (40-50.4 Gy) to the tumor bed and some received concurrent 5-fluorouracil (5-FU) as a radiosensitizer. Comparison of these patients with 17 patients who underwent surgical resection alone showed a trend toward better locoregional control with adjuvant radiotherapy, but there was no advantage in survival. Distant metastasis to the liver, peritoneum, and pleura was the dominant failure pattern in this group of patients.

Barton and Copeland reported on the M.D. Anderson Cancer Center experience of using postoperative chemotherapy for carcinoma of the ampulla of Vater. Seventeen patients received a variety of chemotherapeutic regimens (5-FU was used in combination with doxorubicin, carmustine, vincristine, methyl-lomustine, or mitomycin-C). Although no analysis was presented, the authors concluded that "no combination of drugs appeared to prolong life."[29]

Sikora and colleagues presented their experience from a hospital in India in a retrospective review. Patients who underwent a pancreaticoduodenectomy with adjuvant chemotherapy and radiation did not do any better than the group treated with surgery alone.[30]

Zhou et al reviewed the records of 111 patients at Johns Hopkins who underwent curative surgery for ampullary adenocarcinoma, 45% of whom also received adjuvant chemotherapy and radiation. In these patients, the improvement in survival with adjuvant treatment was not statistically significant (median overall survival: 21.6 vs. 13.0 months, P=0.092).[31]

In a retrospective review, Chan and colleagues reported that 13 patients who received adjuvant chemotherapy (predominantly involving 5-FU, mitomycin-C, and doxorubicin) had a significantly better survival than 16 patients who underwent resection only.[32]

Yeung and colleagues used neoadjuvant chemoradiotherapy for 20 patients with presumed carcinoma of the head of the pancreas, including 4 patients with duodenal/ampullary carcinomas. Interestingly, no residual tumor was found in pancreaticoduodenectomy specimens of the 4 patients thought to have had ampullary/duodenal carcinomas.[33]

At Stanford University, all cases of periampullary carcinoma are discussed and reviewed in detail by a multidisciplinary team that includes surgical oncologists, medical oncologists, radiation oncologists, a pathologist, a gastroenterologist, and a radiologist. All resected tumors are reviewed. Patients with tumors with poor prognostic features (eg, involved surgical margins, lymph nodes, invasion of the pancreas, perineural invasion, or poor histologic grade) are enrolled in a single-arm investigational protocol to receive adjuvant radiotherapy (45 Gy) and concurrent protracted venous infusion of 5-FU (225 mg/m2/d) during the entire treatment course.

Patients with carcinoma of the ampulla of Vater may benefit from recent advances in the treatment planning and delivery of adjuvant and definitive radiotherapy for patients with pancreatic cancer, which have produced modest gains in survival.

Pancreaticoduodenectomy is the procedure of choice for patients with resectable disease, but local recurrence plagues all surgical series, particularly when the pancreas has been invaded or lymph node metastases are discovered. In fact, whether major resection impacts survival in the setting of disease spread to the lymph nodes remains unclear. Postoperative irradiation of at least 45 Gy with 5-FU as a radiosensitizer is a reasonable treatment and reduces local recurrence in pancreatic cancer.

Treatment of Unresectable Disease

For patients with unresectable ampillary carcinoma, endoscopic stenting to achieve biliary decompression is an appropriate palliative procedure. Endoscopic palliation may also be performed for duodenal obstruction with expandable metal stents. Similarly, a palliative bypass may be performed for tumors found to be unresectable intraoperatively.

No established answer exists to the question of further therapy. Very little has been published on adjuvant treatment for locally advanced and advanced ampullary carcinoma. Confining the therapeutic approach to relief of symptoms is reasonable.

Given the paucity of effective standard treatment options, encourage patients to enroll in clinical trials. Radiotherapy, chemotherapy, and chemoradiotherapy have been tried, but response rates probably are low, and an effect on survival is questionable.

Further Outpatient Care

Follow-up guidelines are not well established for ampullary carcinoma. Reasonable practice includes blood studies, chest radiograph, and CT scan of the abdomen and/or pelvis every 6 months.

If treatment ultimately fails, it often does so within 5 years. Unfortunately, good salvage therapies do not yet exist. Palliative chemotherapeutic agents and effective medications for pain relief exist.

 

Prognosis

Reviews of single-institution surgical experiences of ampullary cancer have focused on the identification of histopathologic features associated with prognosis and survival. Retrospective review, small patient numbers, and long periods of enrollment limit what can be learned from these studies. However, common themes emerge from these published clinicopathologic analyses.[34]

Survival after surgical resection is related to the extent of local invasion of the primary lesion, lymph node involvement, vascular invasion, perineural invasion, cellular differentiation, and uninvolved surgical margins. Even a single lymph node with evidence of metastatic carcinoma portends a poor outcome with surgery alone. Exactly which factors are truly independent remains controversial.

El-Ghazzawy et al reviewed experiences in the US Department of Veterans Affairs hospitals from 1987-1991, during which time 123 patients were diagnosed with ampullary cancer. In the group that underwent surgical resection, perineural invasion, microlymphatic invasion, vascular invasion, or tumor differentiation did not independently influence survival when the tumors were controlled for stage.[16]

Yamaguchi et al compared 18 variables among 8 long-term survivors and 12 short-term survivors with ampullary cancer and found that only perineural invasion and histologic grade were significant.[35]

In a retrospective review of 46 consecutive cases of ampullary carcinoma, multivariate analysis by Sudo et al showed perineural invasion to be a significant independent predictor of poor prognosis (P = 0.024). On univariate analysis, other significant predictors of poor prognosis were T3 and T4 tumors (ie, pancreatic parenchymal invasion) (P < 0.001) and lymph node metastasis (P = 0.01).[36]

Multivariate analysis of 302 cases by Lowe et al also showed that perineural invasion is associated with lower survival (hazard ratio [HR] 4.62, 95% confidence interval [CI] 1.11-19.21), as was N1 disease (HR 4.50, CI 1.16-17.40).[37]

A retrospective study of 50 patients by Uchida et al found that patients with preoperative jaundice had poorer survival than those without jaundice (5-year survival 57.2% vs. 100%, respectively, P < 0.01).[38]

Similarly, Carter et al reported that patients with pancreaticobiliary ampullary adenocarcinomas, whose survival was worse than that of patients whose tumors had intestinal histology, were more likely to present with jaundice. This study also drew similarities in patterns of behavior based on histologic subtype, noting that intestinal ampullary adenocarcinomas behaved similarly to their duodenal counterparts, whereas pancreaticobiliary ampullary cancers were generally more aggressive and behaved like pancreatic adenocarcinomas.[3]

In a series from Johns Hopkins, operative blood transfusions conferred a poorer 5-year survival rate on univariate analysis but not on multivariate analysis.[19]

Akwari et al noted that papillary histologic features portended a more favorable prognosis, with a reported 40% survival rate at 5 years, versus only 16% in those with invasive lesions.[39] The Cleveland Clinic experience also confirmed the favorable nature of papillary histology. Table 3 summarizes the outcomes for patients with involved lymph nodes.

Table 3. Summary of 5-Year Survival After Resection for Lymph Node Negative and Positive Carcinoma of the Ampulla of Vater



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In a study of 37 patients, Haruki et al reported that the preoperative neutrophil-to-lymphocyte ratio (NLR) is an independent and significant indicator of long-term outcome after pancreaticoduodenectomy for carcinoma of the ampulla of Vater. An NLR ≥3 was a significant predictor of reduced overall survival (p=0.026).[41]

Patients with ampullary tumors have an overall better prognosis than those with pancreatic cancer and studies have demonstrated better survival after surgical resection for ampullary cancer. Ampullary tumors are more likely to result in biliary obstruction earlier in their course, and therefore tend to present at an earlier stage compared to most pancreatic cancers.[1]

Allema et al reported a 5-year overall survival rate of 50% in patients who underwent resection (subtotal or total pancreaticoduodenectomy) for ampullary cancer. Additionally, This series demonstrated that involvement of resection margins was the strongest prognostic factor for overall survival: patients with negative margins at resection had 5-year survival rates of up to 60%, compared with 15% in patients with positive margins (p<0.001).[17]

Patterns of failure

Unfortunately, most patients with carcinoma of the ampulla of Vater die of recurrent disease. Treatment fails in nearly 70% of patients with poor prognostic features, and these patients ultimately die of their disease.

Kopelson and associates described regional nodal recurrences in 3 of 12 patients with ampullary cancers following potentially curative resection. From pooled data on 80 patients with ampullary cancer, they found that 54% developed locoregional recurrence.[42]

Author

Ayana Allard-Picou, MD, Fellow in Surgical Oncology, Department of Surgery, Roger Williams Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Abdul Saied Calvino, MD, Assistant Professor of Surgery, Boston University School of Medicine; Associate Program Director, Complex Surgical Oncology Fellowship, Coordinator of General Surgery Residents, Surgical Oncology Attending, Department of Surgery, Roger Williams Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Benjamin Movsas, MD,

Disclosure: Nothing to disclose.

Chief Editor

N Joseph Espat, MD, MS, FACS, Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center

Disclosure: Nothing to disclose.

Additional Contributors

Clarence Sarkodee Adoo, MD, FACP, Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Nothing to disclose.

Vivek K Mehta, MD, Radiation Oncologist, Director, Center for Advanced Targeted Radiotherapies, Department of Radiation Oncology, Swedish Cancer Institute

Disclosure: Nothing to disclose.

Acknowledgements

Coauthor(s): George Fisher, MD, PhD, Associate Professor, Department of Internal Medicine, Division of Medical Oncology, Stanford University School of Medicine

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Stage T N M
Stage 0TisN0M0
Stage IAT1N0M0
Stage IBT2N0M0
Stage IIAT3N0M0
Stage IIBT1-T3N1M0
Stage IIIT4Any NM0
Stage IVAny TAny NM1
Institution Year Patients, # Resected, # Mortality Rate, % 5-Year Survival Rate, %
Cleveland Clinic[11] 1950-19845959837
Leicester Royal Infirmary, United Kingdom[12] 1972-198452241356
University of Alabama[13] 1953-198824241361
Mayo Clinic[14] 1965-19891041045.734
Montebelluna Hospital, Italy[15] 1971-19903631356
Veterans Affairs hospitals[16] 1971-1993123641420
Academic Medical Center, Amsterdam[17] 1984-19926762650
Hanover Hospital, Germany[18] 1971-19938785938
Johns Hopkins[19] 1969-1996120106438
Memorial Sloan-Kettering[20] 1983-1995123101544
Catholic University, Italy[21] 1981-20029464964
Institution Node-Negative, % (#) Node-Positive, % (#) P Value
University of Alabama at Birmingham[13] 78 (19)50 (5)Not significant
Mayo Clinic, Minnesota[14] 43 (53)16 (50).001
Montebelluna Hospital, Italy[15] 64 (22)0 (9).36
Academic Medical Center, Amsterdam[17] 59 (32)41 (35).05
Niigata University, Japan[22] 81 (17)41 (18)< .01
Johns Hopkins, Baltimore[19] 43 (53)31 (50).05
Kanazawa University Hospital, Japan[23] 74 (21)31 (15)< .05
Memorial Sloan- Kettering, New York[20] 55 (55)30 (46).04
Loyola University, Chicago[40] 78 (27)25 (24)< 0.05